1. Field of the Invention
This invention relates generally to an instrument using room-temperature sensors that measure magnetic susceptibility variations in the body of a patient. In particular, the instrument can noninvasively monitor ferromagnetic foreign bodies that may become lodged in a patient.
2. Background Art
There is a need for an accurate, noninvasive method to detect the presence of ferromagnetic foreign bodies in a patient who is being considered for magnetic resonance imaging.
As a matter of interest, biomagnetic susceptometry is a diagnostic procedure that involves noninvasive, radiation-free, direct, and accurate, measurement of the magnetic susceptibility of organs and tissue within a human or animal body. For instance, biomagnetic susceptometry can be used to measure human iron stores contained in the liver, see Harris, J. W., et al. (1978), Assessment of human iron stores by magnetic susceptibility measurements, Clin. Res. 26, 540A.; Brittenham, G. M., et al. (1993), Hepatic iron stores and plasma ferritin concentration in patients with sickle cell anemia and thalassemia major, Amer. J. Hematology 42, 85; Brittenham, G. M., et al. (1982), Magnetic susceptibility of human iron stores, New England J. Med., 307, 167 1.; Fischer, R., et al. (1992), Liver iron quantification in the diagnosis and therapy control of iron overload patients, Biomagnetism: Clinical. Aspects, M. Hoke, et al., eds., Elsevier, Amsterdam, p. 585., 1992; Fischer, R., et al. (1989), in Advances In Biomagnetism, S. J. Williamson, et al., eds., Plenum, New York, p. 501. Paulson. D. N., et al. (1991), Biomagnetic susceptometer with SQUID instrumentation, IEEE Trans. Magnetics 27, 3249.; and Nielsen, P., et al. (1995), Liver iron stores in patients with secondary hemosideroses under iron chelation therapy with deferoxamine or deferiprone, Br. J. Hematol. 91, 827.
Unfortunately, instruments based on Superconducting Quantum Interference Devices (SQUIDs), are complex and expensive. They also use liquid helium, leading to significant operating costs and supply problems. Only a few such devices are in use worldwide presently due to their complexity and expense.
SQUIDs based on the recently developed High-Temperature Superconductors (HTS) could, in principle, reduce the cost of magnetic suceptometry. HTS SQUIDs, which can operate at liquid-nitrogen temperatures, would reduce operating costs, and some of the equipment costs, compared to SQUID devices operating at liquid helium temperatures. However, even at liquid-nitrogen temperatures, the operating costs would be higher than those of ordinary instruments operating at room temperature. Moreover, HTS-SQUIDs are expensive to construct and use, because of the difficulty and low yield of the fabrication process. The difficulties, and the costs, are compounded because these devices are vulnerable to moisture, thermal cycling, and static electrical discharge. HTS-SQUIDs also require the same expensive electronics as conventional SQUIDs.
The present instrument obviates the need for cryogenically cooled SQUIDs by providing operational use at room temperature, making for much less expensive fabrication and use. The instrument allows, generally, for measurements of variations of magnetic susceptibility in a patient and, in particular, for an accurate and inexpensive way of detecting areas of increased magnetic susceptibility in patients. In addition, certain improvements introduced in this invention are applicable to all types of magnetic susceptibility measurements.
A key problem with the magnetic susceptibility method is that the patient""s body tissues have their own magnetic susceptibility response, which is superimposed upon the response due to the FFB. To detect the smallest possible FFBs, it would be advantageous to distinguish the signature of the FFB, in the presence of this background response due to body tissues.
U.S. Pat. No. 5,408,178 to Wikswo et. al. describes an apparatus and method for imaging the structure of diamagnetic and paramagnetic objects. The Wikswo et al. method involves applying a magnetic field to a specimen, and measuring the resulting magnetic susceptibility response. Specifically, the Wikswo method attempts to image, or map, the magnetic susceptibility variations within a specimen composed of paramagnetic or diamagnetic material. Wikswo inverts a set of equations, using the measured response as a function of sensor position as well as applied-field direction and measured-field direction, to map out the magnetic susceptibility distribution of the paramagnetic or diamagnetic material within the specimen itself.
The method of the present invention and that of Wikswo et al. make different kinds of measurements and process the data in different ways, to achieve very different results. Specifically, the Wikswo et al. method attempts to image, or map, the magnetic susceptibility variations within a specimen composed of paramagnetic, or diamagnetic material. The present method cancels out the response of paramagnetic or diamagnetic material, to more readily detect the presence of a ferromagnetic foreign body within the specimen. The present method exploits the symmetry properties of the response, as a function of the applied-field and measured-field directions, in order to cancel the response of paramagnetic and diamagnetic material within the specimen, and thus detect the presence of a ferromagnetic foreign body. Wikswo et al. invert a set of equations, using the measured response as a function of sensor position as well as applied-field direction and measured-field direction, in an attempt to map out the magnetic susceptibility distribution of the paramagnetic or diamagnetic material within the specimen itself.
This invention provides a practical method and apparatus for measuring variations of magnetic susceptibilities in a patient, and, in particular, preferably localized areas of increased magnetic susceptibility. The probing instrument""s distal end assembly includes a room temperature functioning magnetic sensor that can detect the characteristic magnetic response from tissue to a magnetic field supplied by an applied-field coil, or a permanent magnet, that is also part of the instrument""s distal end assembly. The applied field coil can be an alternating current (AC) coil. The magnetic susceptibility measurements have sufficient resolution to monitor small variations in magnetic susceptibility within the patient, when the instrument is placed external to the patient.
The applied field may be produced using an applied field coil or a permanent magnet. The use of an applied field coil is preferred for a number of reasons. First, it lends itself to the application of an alternating magnetic field. The use of an alternating magnetic field reduces sensor noise, reduces noise due to ambient magnetic fields, and facilitates the modulation of the sensor-sample distance in order to reduce the effects of temperature drift in the sensing apparatus. Also, the use of an applied-field coil, or coils, lends itself to the cancellation of the signal due to the applied magnetic field.
An alternative embodiment is to use a permanent magnet to produce the applied magnetic field. A permanent magnet produces a constant DC field, which lacks many of the advantages of an alternating field. In principle, one could produce an alternating magnetic field by appropriate movement, such as reciprocating motion, of one or more permanent magnets.
The magnetic sensor can be, but is not necessarily limited to, a magnetoresistive sensor, including giant magnetoresistive and spin-dependent tunneling sensors, a fluxgate magnetometer, or a magneto-inductive sensor. In some cases, the noise in the magnetic field measurements can be reduced by using an induction coil sensor, which detects a changing magnetic field by measuring the voltage induced in a coil of electrically conductive wire.
The applied field coil dimensions are such that an applied field is optimized for maximum response from localized areas of interest in the body. In particular, the instrument is preferably designed for detecting the presence of ferromagnetic foreign bodies (FFBs) in a patient. For this application, the applied field coil dimensions are optimized to maximize the magnetic susceptibility response from the item of interest and minimize effects caused by the overlying tissue. To minimize noise introduced in the magnetic measurements due to fluctuations in the applied field, the applied-field coil and/or magnetic sensors are configured so as to cancel the signal due to the applied field. Both the real and imaginary parts of the applied field signal are canceled. This result can be achieved by designing the applied-field coil so that the field is canceled at the position of the sensor. Alternatively, the magnetic sensor itself can be designed as a magnetic gradiometer, so as to cancel the signal due to the applied field.
The probe instrument""s distal end detector assembly includes one or more applied field coils and magnetic sensors, in a geometry designed to cancel the applied-field signal and to maximize the signal due to the objects of interest in relation to that of overlying body tissue. The magnetic sensor is preferably a magnetoresistive (MR) sensor or an induction coil. In general, MR sensors are preferred where the frequency of the AC field is low, and where it is necessary to sense the magnetic field within a relatively small volume, while induction coils are preferred where the frequency is high, and it is possible to average the magnetic field over a relatively large volume or surface area. When an MR sensor is used, a feedback coil can be mounted on the sensor, which xe2x80x9clocksxe2x80x9d the sensor at its optimum operating point by applying a compensating field to cancel changes in the ambient field, thus maintaining a constant sensitivity of the detector assembly. This feedback technique is desirable in some cases to maintain constant responsivity and high linearity, especially in instances where it is necessary to measure small changes in magnetic field in the presence of much larger background magnetic fields.
The probing instrument""s magnetic sensor control electronics, an applied field source signal generator, a lock-in amplifier, an audio amplifier, and an FFT spectrum analyzer or equivalent computer device for signal analysis can all be incorporated in a single medical instrument housing for field use. A computer can be used to perform the functions of the signal generator, the lock-in amplifier, and/or the FFT spectrum analyzer. The computer approach may reduce cost, especially in cases where measurements with multiple sensors are required.
A physician uses the probing instrument by positioning the probe""s distal end adjacent to an area of interest, such as the eye/orbit, and the probe instrument then analyzes the observed signal, and outputs data corresponding to material of interest.
Further, according to the present invention, the magnetic responses of surrounding body tissues are canceled out, allowing the presence of a ferromagnetic foreign body to be detected easily. This tissue background cancellation can be achieved by two methods. The first method determines whether the measured magnetic field response falls outside a normal range determined from a statistical analysis of measurements on a population of subjects. This analysis exploits statistical regularities in the responses of normal subjects, including, for example, the similarity in response between the left and the right sides of the patient""s head.
The second method determines whether the magnetic field response exhibits certain mathematical symmetries that reflect the weak, isotropic magnetization properties characteristic of biological tissues.
The second method applies uniform magnetic fields to the target region, in each of three orthogonal directions. For each direction of the applied field, the magnetic field response of the specimen is measured. Preferably, the magnetic field in each of three orthogonal directions is measured, for each direction of the applied magnetic field. However, useful information can be obtained by measuring the magnetic field solely in the direction of the applied field. Other combinations of applied field and measured field are possible as well. Measuring the magnetic field in all three directions maximizes the probability of detecting a ferromagnetic foreign body, regardless of its orientation, location, and shape. All of these magnetic-field measurements are made at the same sensor location. The results are expressed as a matrix or table of values, where each entry By represents the magnetic field response measured in the direction i, while applying the magnetic field in the direction j. If the specimen contains only paramagnetic or diamagnetic material, that is, material whose magnetization is proportional to, but weak in comparison to, the applied field, this matrix will be symmetric and traceless, that is, Bijxe2x88x92Bji=O, and B11+B22+B33=0. Using these symmetry properties, one can cancel out the response of the diamagnetic and paramagnetic material within the specimen, leaving only the response due to a ferromagnetic foreign body contained within the specimen. In the present method, the applied magnetic field is uniform and unidirectional, in order that the matrix By have the required symmetry properties.
Depending on the particular combination of applied and measured fields that is used, it may occur that a ferromagnetic foreign body with a particular combination of shape, orientation, and location may not be revealed by examining the quantities, Bijxe2x88x92Bji, and B11+B22+B33. In order to avoid such situations, it is desirable to repeat the entire measurement sequence described above, varying the sensor location with respect to the patient. It should be noted that this variation of the sensor location has a different purpose in the present method than in the method of Wikswo et al. Wikswo et al. measure the magnetic field response at a plurality of sensor locations, in order to derive a map of the spatial variation of magnetic susceptibility within the sampled region. In the present invention, the sensor location is varied in order to change the spatial relationship between the ferromagnetic foreign body and the magnetic sensor, or sensors, so as to ensure that at least one of the quantities, Bijxe2x88x92Bji, or B11+B22+B33, is nonzero for at least one sensor location. As indicated previously, the present invention does not rely on mapping magnetic susceptibility variations within the sampled region. Rather, the present approach is to cancel the response of the host tissue without canceling the response of the ferromagnetic foreign body. This affords a simpler solution to the problem of FFB detection than the method of Wikswo et al.
As will be discussed below under the heading, xe2x80x9cData Analysis Combining both Discrimination Techniques,xe2x80x9d the two methods described above can be combined into a single statistical analysis framework.
In addition to these background discrimination techniques, the variability of the magnetic response of the host can be minimized by inserting between the patient and the sensing instrument a bag, or other compliant container filled with water, a gel, or other material, which will conform to the shape of the sensed region, such as the eye/orbit, and which approximates the magnetic susceptibility of the sensed body region. Water-bag techniques have been used previously in the context of liver iron measurements. However, the present invention encompasses a novel water-bag method which has significant advantages when used with a room temperature sensor system.
Further, with any of these discrimination techniques, telemedicine can be employed to enhance the functionality of the techniques. The preferred vehicle for telemedicine is the Internet. Artificial intelligence modalities, including neural networks and other expert systems, such as rule-based systems, can also be employed, providing instantaneous auto-interpretation of test results. Real time interactive feedback is thus provided between a remote test instrument and a central computer processing system, thereby helping to ensure patient cooperation and reliable data acquisition.
The novel features of this invention, as well as the invention itself, will be best understood from the attached drawings, taken along with the following description, in which similar reference characters refer to similar parts, and in which: